Bottom Line:
Chronic stress increased also expression of Timp1 and Ppbp that are involved in reaction to vascular injury.Acute stress did not affect expression of hemoglobin genes but it altered expression of Fam107a (Drr1) and Agxt2l1 (Etnppl) that have been implicated in psychiatric diseases.The observed up-regulation of genes associated with vascular system and brain injury suggests that stressful social encounters may affect brain function through the stress-induced dysfunction of the vascular system.

Background: In order to better understand the effects of social stress on the prefrontal cortex, we investigated gene expression in mice subjected to acute and repeated social encounters of different duration using microarrays.

Results: The most important finding was identification of hemoglobin genes (Hbb-b1, Hbb-b2, Hba-a1, Hba-a2, Beta-S) as potential markers of chronic social stress in mice. Expression of these genes was progressively increased in animals subjected to 8 and 13 days of repeated stress and was correlated with altered expression of Mgp (Mglap), Fbln1, 1500015O10Rik (Ecrg4), SLC16A10, and Mndal. Chronic stress increased also expression of Timp1 and Ppbp that are involved in reaction to vascular injury. Acute stress did not affect expression of hemoglobin genes but it altered expression of Fam107a (Drr1) and Agxt2l1 (Etnppl) that have been implicated in psychiatric diseases.

Conclusions: The observed up-regulation of genes associated with vascular system and brain injury suggests that stressful social encounters may affect brain function through the stress-induced dysfunction of the vascular system.

Mentions:
The analysis of microarray data revealed significant differences in transcriptomic profiles between stressed and control mice at all of the studied time points (Additional file 1). Although we detected 662 transcripts that were up- or down-regulated by different stress regimes (Table 3), only few genes were significantly regulated at more than one treatment group (Figure 6). The analysis revealed that significantly regulated genes could be grouped into 11 clusters characterized by distinct pattern of expression (Figures 7 and 8; Additional file 1). The most consistent transcriptomic changes that correlated with duration of stress were found in cluster 7 (Figure 7). The core of this cluster contained highly correlated genes coding for hemoglobin (Hbb-b1, Hbb-b2, Hba-a1, Hba-a2, Beta-S) and two other genes involved in heme synthesis (Alas2) and vascular homeostasis (Mgp). Expression of these genes was not altered by acute stress, but was progressively increased in animals subjected to 8 and 13 days of stress (Figure 7, Additional file 1). Cluster 7, additionally, contained 14 genes that were up- or down- regulated only after 13 days of stress (Figure 7). Consistent pattern of expression was also found in cluster 9, which contained transcripts of unknown functions that were down-regulated after acute and chronic stress (Figure 7). This cluster contained also 4 other transcripts that were significantly up-regulated (Agxt2l1, Clcnka, Fam107a) or down-regulated (Abpa) but only after acute stress (Figure 7). The remaining clusters displayed much less consistent pattern characterized by high variability between the different pools of RNA (Figure 8). In most cases, genes belonging to these clusters were significantly regulated only in one of the stress groups and, frequently, large differences were restricted to one out of three pools from the group. Exceptions were Timp1 (cluster 10), which was up-regulated in all 3 pools from the chronic stress group (13 days of stress), and Tgtp2 (cluster 11), which was down-regulated in all 3 pools from the recovery group (Figure 8).Table 3

Mentions:
The analysis of microarray data revealed significant differences in transcriptomic profiles between stressed and control mice at all of the studied time points (Additional file 1). Although we detected 662 transcripts that were up- or down-regulated by different stress regimes (Table 3), only few genes were significantly regulated at more than one treatment group (Figure 6). The analysis revealed that significantly regulated genes could be grouped into 11 clusters characterized by distinct pattern of expression (Figures 7 and 8; Additional file 1). The most consistent transcriptomic changes that correlated with duration of stress were found in cluster 7 (Figure 7). The core of this cluster contained highly correlated genes coding for hemoglobin (Hbb-b1, Hbb-b2, Hba-a1, Hba-a2, Beta-S) and two other genes involved in heme synthesis (Alas2) and vascular homeostasis (Mgp). Expression of these genes was not altered by acute stress, but was progressively increased in animals subjected to 8 and 13 days of stress (Figure 7, Additional file 1). Cluster 7, additionally, contained 14 genes that were up- or down- regulated only after 13 days of stress (Figure 7). Consistent pattern of expression was also found in cluster 9, which contained transcripts of unknown functions that were down-regulated after acute and chronic stress (Figure 7). This cluster contained also 4 other transcripts that were significantly up-regulated (Agxt2l1, Clcnka, Fam107a) or down-regulated (Abpa) but only after acute stress (Figure 7). The remaining clusters displayed much less consistent pattern characterized by high variability between the different pools of RNA (Figure 8). In most cases, genes belonging to these clusters were significantly regulated only in one of the stress groups and, frequently, large differences were restricted to one out of three pools from the group. Exceptions were Timp1 (cluster 10), which was up-regulated in all 3 pools from the chronic stress group (13 days of stress), and Tgtp2 (cluster 11), which was down-regulated in all 3 pools from the recovery group (Figure 8).Table 3

Bottom Line:
Chronic stress increased also expression of Timp1 and Ppbp that are involved in reaction to vascular injury.Acute stress did not affect expression of hemoglobin genes but it altered expression of Fam107a (Drr1) and Agxt2l1 (Etnppl) that have been implicated in psychiatric diseases.The observed up-regulation of genes associated with vascular system and brain injury suggests that stressful social encounters may affect brain function through the stress-induced dysfunction of the vascular system.

Background: In order to better understand the effects of social stress on the prefrontal cortex, we investigated gene expression in mice subjected to acute and repeated social encounters of different duration using microarrays.

Results: The most important finding was identification of hemoglobin genes (Hbb-b1, Hbb-b2, Hba-a1, Hba-a2, Beta-S) as potential markers of chronic social stress in mice. Expression of these genes was progressively increased in animals subjected to 8 and 13 days of repeated stress and was correlated with altered expression of Mgp (Mglap), Fbln1, 1500015O10Rik (Ecrg4), SLC16A10, and Mndal. Chronic stress increased also expression of Timp1 and Ppbp that are involved in reaction to vascular injury. Acute stress did not affect expression of hemoglobin genes but it altered expression of Fam107a (Drr1) and Agxt2l1 (Etnppl) that have been implicated in psychiatric diseases.

Conclusions: The observed up-regulation of genes associated with vascular system and brain injury suggests that stressful social encounters may affect brain function through the stress-induced dysfunction of the vascular system.